Stratification of risk to quantify prognosis Other risk factors and disease history Normal SBP 120129 or DBP 8084

Average risk Blood pressure (mmHg) High normal SBP 130139 or DBP 8589 Average risk Grade 1 HT Grade 2 HT Grade 3 HT

SBP 140159 SBP 160179 SBP > 180 or DBP 9099 or DBP 100109 or DBP > 110 No other risk Low added risk Moderate added High added factors risk risk 12 risk factors Low added risk Low added risk Moderate added Moderate added Very high risk risk added risk 3 or more risk Moderate added High added High added High added risk Very high factors, MS, risk risk risk added risk OD or diabetes Established High added Very high Very high Very high Very high cardiovascular risk added risk added risk added risk added risk or renal disease OD - subclinical organ damage; SBP - systolic blood pressure; DBP - diastolic blood pressure, MS metabolic syndrome The terms low, moderate, high and very high added risk are calibrated to indicate an approximate absolute 10-year risk of cardiovascular disease of <15%, 1520%, 2030% and >30%, respectively, according to Framingham criteria, or an approximate absolute risk of fatal cardiovascular disease <4%, 45%, 58%, and >8% according to the SCORE chart.

FACTORS INFLUENCING PROGNOSIS Risk factors Subclinical organ damage Diabetes (OD) mellitus 1. Systolic and diastolic 1. Left ventricular Fasting plasma BP levels hypertrophy glucose 7.0 2. Levels of pulse pressure electrocardiogram: mmol/l (126 (in the elderly) mg/dl) on SokolowLyons index 3. Age (Men>55 years, (SV1+RV5-6) >38 mm; repeated Women >65 years) measurements or Cornell >2440 mm x ms; 4. Smoking Postprandial echocardiogram: 5. Dyslipidaemia: LVMI=left ventricular mass plasma glucose >11.0 mmol/l total cholesterol: index: M>125, W>110 g/m2 (>198 mg/dl) >5.0 mmol/l 2. Vessels (>190 mg/dl), or Ultrasound evidence of LDL-cholesterol: carotid wall thickening >3.0 mmol/l (carotid intima-media (>115 mg/dl), or thickness > 0.9 mm) or atherosclerotic plaque HDL-cholesterol: M <1.0 mmol/l Carotid-femoral pulse (<40 mg/dl) wave velocity>12 m/s W <1.2 mmol/l Ankle/brachial BP (<46 mg/dl) index<0,9 Triglycerides: 3. Kidney > 1,7 mmol/l Slight increase in serum (150 mg/dl) creatinine

Established cardiovascular or renal disease 1. Cerebrovascular disease: ischaemic stroke; cerebral haemorrhage; transient ischaemic attack 2. Heart disease: myocardial infarction; angina; coronary revascularization; congestive heart failure 3. Renal disease: diabetic nephropathy; renal impairment serum creatinine (M>133 mol/l (>1.5 mg/dl) W>124 mol/l (>1.4 mg/dl) proteinuria (>300 mg/24 h) 4. Peripheral artery disease 5.Advanced retinopathy: haemorrhages or exudates, papilloedema

6.Family history of premature cardiovascular disease (M at age <55 years, W <65 years) 7. Abdominal obesity (waist circumference M > 102 cm, W> 88 cm) 8.Fasting plasma glucose 5,6-6,9 mmol/l (102-125 mg/dl) 9. Abnormal glucose tolerance test

M 115133 mol/l (1.31.5 mg/dl) W 107124 mol/l (1.21.4 mg/dl) Microalbuminuria 30300 mg/24 h; or albumincreatinine ratio M > 22 mg/g (> 2.5 mg/mmol) W >31 mg/g (> 3.5 mg/mmol) Low estimated glomerular filtration rate (MDRD formula): <60 ml/min/1,73 m2 or Low creatinine clearance (Cockroft-Gault formula): <60 ml/min

INITIATION OF ANTIHYPERTENSIVE TREATMENT.

Normal BP Other risk SBP 120-129 factors OD or DBP 80-84 or disease No other No BP risk factors intervention High normal BP SBP 130-139 or DBP 85-89 Grade 1 HT SBP 140-159 or DBP 90-99 Grade 2 HT SBP 160-179 or DBP 100-109 Grade 3 HT SBP > 180 or DBP>110

1-2 risk factors

Lifestyle changes

>3 risk Lifestyle changes factors, MS or OD Diabetes Lifestyle changes

No BP intervention Lifestyle changes for several months then drug treatment if BP uncontrolled Lifestyle changes Lifestyle changes for several weeks then drug treatment if BP uncontrolled Lifestyle changes Lifestyle changes and consider drug +Drug treatment treatment

Lifestyle changes Lifestyle changes for several weeks + Immediate drug then drug treatment treatment if BP uncontrolled Lifestyle changes Lifestyle changes for several weeks + Immediate drug then drug treatment treatment if BP uncontrolled Lifestyle changes + Drug treatment Lifestyle changes + Immediate drug treatment Lifestyle changes + Immediate drug treatment

Lifestyle changes + Lifestyle changes Lifestyle changes Drug treatment +Drug treatment + Drug treatment

Established Lifestyle changes Lifestyle changes CV or + Immediate drug + Immediate drug + renal treatment treatment disease

Lifestyle changes Lifestyle changes Lifestyle changes + Immediate + Immediate drug + Immediate drug drug treatment treatment treatment

ANTIHYPERTENSIVE TREATMENT: PREFERRED DRUGS

LVH Asympt. atherosclerosis Microalbuminuria Renal dysfunction Previous stroke Previous Ml Angina pectoris Heart failure

Subclinical organ damage ACEl, CA, ARB CA, ACEl ACEl, ARB ACEl, ARB Clinical event any BP lowering agent BB, ACEl, ARB BB, CA Diuretics, BB, ACEl, ARB, antialdosterone agents - ARB, ACEl - BB, non-dihydropiridine CA ACEl, ARB, loop diuretics CA Condition Diuretics, CA ACEl, ARB, CA, modulators of imidazoline receptors ACEl, ARB CA, methyldopa, BB Diuretics, CA

Atrial fibrillation: - Recurrent - Permanent ESRD/proteinuria Peripheral artery disease ISH (elderly) Metabolic syndrome Diabetes mellitus Pregnancy Blacks

Abbreviations: LVH: left ventricular hypertrophy; ISH: isolated systolic hypertension; ESRD: renal failure; ACEl: ACE inhibitors; ARB: angiotensin receptor antagonists; CA: calcium antagonists; BB: b-blockers Aliskiren, a new drug that is targeting the renin system at its point of activation is already available in the USA and may soon be made available in Europe. This drug has been shown to effectively lower blood pressure in hypertension, both alone and in combination with a thiazide diuretic, and also to have an antiproteinuric effect in pre-dinical studies. It has been suggested that renin may have effects not connected to the classical renin-angiotensin cascade and be a prognostic factor independent of angiotensin II production. Conclusive evidence that this is the case as well as data on the cardiovascular protective effects of renin inhibition is not yet available.

Blood pressure thresholds (mmHg) for definition of hypertension with different types of measurement SBP, DBP, systolic blood pressure diastolic blood pressure Office or clinic 140 90 24-hour ambulatory: 125-130 80 - day 130-135 85 -night 120 70 Home (self) 130-135 85 Isolated office hypertension) Diagnosis Investigation Prescription (or clinic)

hypertension

(so-called

whitecoat

Office BP > 140/90 mmHg (at several visits); 24 h ambulatory BP <125/80 mmHg. Possible metabolic risk factors; possible target organ damage Lifestyle changes and close follow-up; drug treatment if evidence of target organ damage

Blood pressure measurement 1. Blood pressure values measured in the doctors office or the clinic should commonly be used as reference. 2. Twenty-four-hour ambulatory blood pressure monitoring may be considered of additional clinical value, when: considerable variability of office blood pressure is found over the same or different visits; high office blood pressure is measured in subjects otherwise at low global cardiovascular risk; there is marked discrepancy between blood pressure values measured in the office and at home; resistance to drug treatment is suspected; research is involved. 3. Self-measurement of blood pressure at home should be encouraged in order to: provide more information for the doctors decision; improve patients adherence to treatment regimens. 4. Self-measurement of blood pressure at home should be discouraged whenever: it causes patients anxiety; it induces self-modification of the treatment regimen. 5. Normal values are different for office, ambulatory and home blood pressure.

Physical examination for secondary hypertension and organ damage Signs suggesting secondary hypertension and organ damage Features of Cushing syndrome. Skin stigmata of neurofibromatosis (phaeochromocytoma). Palpation of enlarged kidneys (polycistic kidney). Auscultation of abdominal murmurs (renovascular hypertension). Auscultation of precordial or chest murmurs (aortic coarctation or aortic disease). Diminished and delayed femoral and reduced femoral blood pressure (aortic coarctation, aortic disease). Signs of organ damage Brain: murmurs over neck arteries, motor or sensory defects. Retina: funduscopic abnormalities. Heart: location and characteristics of apical impulse, abnormal cardiac rhythms, ventricular gallop, pulmonary rales, dependent oedema. Peripheral arteries: absence, reduction, or asymmetry of pulses, cold extremities, ischaemic skin lesions.

Laboratory investigations
Routine tests Plasma glucose (preferably fasting) Serum total cholesterol Serum high-density lipoprotein (HDL)-cholesterol Fasting serum triglycerides Serum uric acid Serum creatinine Serum potassium Haemoglobin and haematocrit Urinalysis (dipstick test complemented by urinary sediment examination) Electrocardiogram Recommended tests Echocardiogram Carotid (and femoral) ultrasound C-reactive protein Microalbuminuria (essential test in diabetics) Quantitative proteinuria (if dipstick test positive) Funduscopy (in severe hypertension) Extended evaluation (domain of the specialist) Complicated hypertension: tests of cerebral, cardiac and renal function Search for secondary hypertension: measurement of renin, aldosterone, corticosteroids, catecholamines; arteriography; renal and adrenal ultrasound; computer-assisted tomography (CAT); brain magnetic resonance imaging.

Heart Electrocardiography should be part of all routine assessment of subjects with high blood pressure to detect ischaemia, conduction defects and arrhythmias. Its sensitivity in detecting left ventricular hypertrophy is low but, none the less, positivity of the SokolowLyons index (SV1 + RV56 >38 mm) or of the Cornell modified index (> 2440 mmx ms) has been shown to be an independent predictor of cardiovascular events. The Cornell voltage QRS duration product has been used successfully in detecting patients with left ventricular hypertrophy to be included in an intervention trial. Electrocardiography can be used also to detect patterns of ventricular overload (strain), known to indicate more severe risk. Echocardiography is undoubtedly much more sensitive than electrocardiography in diagnosing left ventricular hypertrophy and predicting cardiovascular risk. The availability of echocardiography has increased in Europe, and when treatment decisions are uncertain an echocardiographic examination may help in more precisely classifying the overall risk of the hypertensive patient and in directing therapy. The evaluation should include measurements of interventricular septum and posterior wall thicknesses and of end diastolic left ventricular diameter, with calculation of left ventricular mass according to available formulae. Although the relation between left ventricular mass index and cardiovascular risk is continuous, the threshold of 125 g/m2 for men, and 110 g/m2 for women, is most widely used for conservative estimates of left ventricular hypertrophy. Classification into concentric or eccentric hypertrophy, and concentric remodelling by using the wall to radius ratio (values >0.45 define concentric patterns) have been shown also to have risk-predicting value. Ultrasound methods for quantitatively evaluating the fibrosis component accompanying hypertrophy (echoreflectivity, back scattering) have been described, but, at present, are of research interest only. In addition, echocardiography provides a means of assessing left ventricular systolic function including midwall fractional shortening, which has been proposed as a reliable predictor of cardiovascular events. Furthermore, left ventricular diastolic distensibility (socalled diastolic function) can also be assessed by Doppler measurement of the ratio between the E and A waves of transmitral blood flow (and, more precisely, by adding measurement of early diastolic relaxation time and evaluating patterns of pulmonary vein outflow into the left atrium). There is current interest in whether patterns of so-called diastolic dysfunction can predict onset of dyspnoea and impaired effort tolerance without evidence of systolic dysfunction, frequently occurring in hypertension and in the elderly (so-called diastolic heart failure). Finally, echocardiography can provide evidence of left ventricular wall contraction defects due to ischaemia or previous infarction, and of systolic dysfunction. Other diagnostic cardiac procedures, such as nuclear magnetic resonance, cardiac scintigraphy, exercise testing and coronary angiography are reserved for specific indications (diagnosis of coronary artery disease, cardiomyopathy, etc.).

Kidney The diagnosis of hypertension-induced renal damage is based on the finding of an elevated value of serum creatinine, of a decreased (measured or estimated) creatinine clearance, or the detection of an elevated urinary excretion of albumin below (microalbuminuria) or above (macroalbuminuria) the limit of the usual laboratory methods to detect proteinuria. The presence of mild renal insufficiency has been defined recently as serum creatinine values equal to or above 133 mol/l (1.5 mg/dl) in men and 124 mol/l (1.4 mg/dl) in women, or by the finding of estimated creatinine clearance values below 6070 ml/min. An estimate of creatinine clearance in the absence of 24-h urine collection can be obtained based on prediction equations corrected for age, gender and body size. A slight increase in serum creatinine and urate may sometimes occur when antihypertensive therapy is instituted or intensified, but this should not be taken as a sign of progressive renal deterioration. Hyperuricaemia [defined as a serum urate level in excess of 416 mol/l (7 mg/dl)] is frequently seen in untreated hypertensives and has also been shown to correlate with the existence of nephrosclerosis. While an elevated serum creatinine concentration points to a reduced rate of glomerular filtration, an increased rate of albumin or protein excretion points to a derangement in the glomerular filtration barrier. Microalbuminuria has been shown to predict the development of overt diabetic nephropathy in both type 1 and type 2 diabetics, while the presence of proteinuria generally indicates the existence of established renal parenchymatous damage. In nondiabetic hypertensive patients microalbuminuria, even below the current threshold values, has been shown to predict cardiovascular events, and a continuous relation between urinary albumin excretion and cardiovascular, as well as non-cardiovascular, mortality has recently been found in a general population study. The finding of a deranged renal function in a hypertensive patient, expressed by any of the above parameters, is frequent and constitutes a very potent predictor of future cardiovascular events and death. Therefore, it is recommended that serum creatinine (and possibly also estimated creatinine clearance calculated on the basis of age, gender and body size), serum urate and urinary protein (by dipstick) be measured in all hypertensive patients. Microalbuminuria should be measured in all diabetic patients and, whenever possible, in non-diabetic hypertensives (dipstick-negative patients) by a validated laboratory method on urine samples collected during the night, and preferably related to creatinine excretion (age-adjusted albumin to creatinine ratio).

Goals of treatment The primary goal of treatment of the patient with high blood pressure is to achieve the maximum reduction in the long-term total risk of cardiovascular morbidity and mortality. This requires treatment of all the reversible risk factors identified, including smoking, dyslipidaemia or diabetes, and the appropriate management of associated clinical conditions, as well as treatment of the raised blood pressure per se. On the basis of current evidence from trials, it can be recommended that blood pressure, both systolic and diastolic, be intensively lowered at least below 140/90 mmHg and to definitely lower values, if tolerated, in all hypertensive patients, and below 130/80 mmHg in diabetics, keeping in mind, however, that systolic values below 140 mmHg may be difficult to achieve, particularly in the elderly. Lifestyle changes Lifestyle measures should be instituted whenever appropriate in all patients, including subjects with high normal blood pressure and patients who require drug treatment. The purpose is to lower blood pressure and to control other risk factors and clinical conditions present. The lifestyle measures that are widely agreed to lower blood pressure or cardiovascular risk, and that should be considered, are: Smoking cessation; Weight reduction; Reduction of excessive alcohol intake; Physical exercise; Reduction of salt intake; Increase in fruit and vegetable intake and decrease in saturated and total fat intake.

Monotherapy versus combination therapy In most, if not all, hypertensive patients, therapy should be started gradually, and target blood pressure values achieved progressively through several weeks. To reach target blood pressure, it is likely that a large proportion of patients will require combination therapy with more than one agent. According to the baseline blood pressure and the presence or absence of complications, it appears reasonable to initiate therapy either with a low dose of a single agent or with a low-dose combination of two agents. There are advantages and disadvantages with either approach. The following two-drug combinations have been found to be effective and well tolerated: diuretic and -blocker; diuretic and ACE inhibitor or angiotensin receptor antagonist; calcium antagonist (dihydropyridine) and -blocker; calcium antagonist and ACE inhibitor or angiotensin receptor antagonist; calcium antagonist and diuretic; -blocker and -blocker; other combinations (e.g. with central agents, including 2-adrenoreceptor agonists and imidazoline I2 receptor modulators, or between ACE inhibitors and angiotensin receptor antagonists) can be used if necessary, and three or four drugs may be required in many cases. Choice of antihypertensive drugs The main benefits of antihypertensive therapy are due to lowering of blood pressure per se. There is also evidence that specific drug classes may differ in some effect, or in special groups of patients. Drugs are not equal in terms of adverse disturbances, particularly in individual patients. The major classes of antihypertensive agents diuretics, -blockers, calcium antagonists, ACE inhibitors, angiotensin receptor antagonists are suitable for the initiation and maintenance of therapy. Emphasis on identifying the first class of drugs to be used is probably outdated by the need to use two or more drugs in combination in order to achieve goal blood pressure. Within the array of available evidence, the choice of drugs will be influenced by many factors, including: previous experience of the patient with antihypertensive agents; cost of drugs; risk profile, presence or absence of target organ damage, clinical cardiovascular or renal disease or diabetes; and patients preference.

Antihypertensive therapy in the elderly

There is little doubt from randomized controlled trials that older patients with systolicdiastolic or with isolated systolic hypertension benefit from antihypertensive treatment in terms of reduced cardiovascular morbidity and mortality. Initiation of antihypertensive treatment in elderly patients should follow the general guidelines, but should be particularly gradual, especially in frail individuals. Blood pressure measurement should also be performed in the erect posture, to exclude patients with marked postural hypotension from treatment and to evaluate postural effects of treatment. Many elderly patients will have other risk factors, target organ damage and associated cardiovascular conditions, to which the choice of the first drug should be tailored. Many elderly patients need two or more drugs to control blood pressure, particularly since it is often difficult to lower systolic blood pressure to below 140 mmHg. In subjects aged 80 years and over, a recent metaanalysis concluded that fatal and non-fatal cardiovascular events, but not mortality, are reduced by antihypertensive therapy.

Antihypertensive therapy in diabetics Non-pharmacological measures (particularly weight loss and reduction in salt intake) should be encouraged in all patients with type 2 diabetes, independently of the existing blood pressure. These measures may suffice to normalize blood pressure in patients with high normal or grade 1 hypertension, and can be expected to facilitate blood pressure control by antihypertensive agents. The goal blood pressure to aim at during behavioral or pharmacological therapy is below 130/80 mmHg. To reach this goal, most often combination therapy will be required. It is recommended that all effective and well-tolerated antihypertensive agents are used, generally in combination. Available evidence indicates that Reno protection benefits from the regular inclusion in these combinations of an ACE inhibitor in type 1 diabetes and of an angiotensin receptor antagonist in type 2 diabetes. In type 2 diabetic patients with high normal blood pressure, who may sometimes achieve blood pressure goal by monotherapy, the first drug to be tested should be a blocker of the reninangiotensin system. The finding of microalbuminuria in type 1 or 2 diabetics is an indication for antihypertensive treatment, especially by a blocker of the renin angiotensin system, irrespective of the blood pressure values.

Antihypertensive therapy in patients with deranged renal function Before antihypertensive treatment became available, renal involvement was frequent in patients with essential hypertension. Renal protection in diabetes has two main requirements: strict blood pressure control (<130/80 mmHg and even lower if proteinuria is >1 g/day); lowering proteinuria to values as near to normal as possible. To reduce proteinuria either an angiotensin receptor blocker or an ACE inhibitor is required. To achieve the blood pressure goal, combination therapy is usually required, with addition of a diuretic and a calcium antagonist. To prevent or retard nephrosclerosis in hypertensive non-diabetic patients, blockade of the reninangiotensin system appears more important than attaining very low blood pressure, but evidence is so far restricted to AfroAmerican hypertensives, and suitable studies in other ethnic groups are required. It appears prudent, however, to lower blood pressure intensively in all hypertensive patients with deranged renal function. An integrated therapeutic intervention (antihypertensives, statins, antiplatelet therapy, etc.) frequently has to be considered in patients with renal damage. Causes of resistant hypertension Unsuspected secondary cause. Poor adherence to therapeutic plan. Continued intake of drugs that raise blood pressure. Failure to modify lifestyle including: weight gain; heavy alcohol intake (NB binge drinking). Volume overload due to: inadequate diuretic therapy; progressive renal insufficiency; high sodium intake. Causes of spurious resistant hypertension Isolated office (white-coat) hypertension. Failure to use large cuff on large arm.

Treatment of associated risk factors Lipid-lowering agents All patients up to the age of 80 with active coronary heart disease, peripheral arterial disease, history of ischaemia, stroke and long-standing type 2 diabetes should receive a statin if their total cholesterol is >3.5 mmol/l (135 mg/dl), with the goal of reducing it by about 30%. Patients without overt cardiovascular disease or with recent-onset diabetes, whose estimated 10-year cardiovascular risk is > 20%, should also receive a statin if their total cholesterol is >3.5 mmol/l (135 mg/dl). Antiplatelet therapy Antiplatelet therapy, in particular low-dose aspirin, should be prescribed to patients with previous cardiovascular events, as it has been shown to reduce the risk of stroke and myocardial infarction (provided patients are not at an excessive risk of bleeding). In hypertensive patients, low-dose aspirin has been shown to be beneficial (reduction of myocardial infarction greater than the risk of excess bleeding) in patients older than 50 with an even moderate increase in serum creatinine, or with a 10-year total cardiovascular risk > 20%. In hypertensives, low-dose aspirin administration should be preceded by good blood pressure control.

Renal parenchymal hypertension Renal parenchymal disease is the most common cause of secondary hypertension. The finding of bilateral upper abdominal masses at physical examination is consistent with polycystic kidney disease and should lead to an abdominal ultrasound examination. Renal ultrasound has now almost completely replaced intravenous urography in the anatomical exploration of the kidney. While the latter requires the injection of potentially nephrotoxic contrast medium, ultrasound is non-invasive and provides all the necessary anatomic data about kidney size and shape, cortical thickness, urinary tract obstruction and renal masses. Assessing the presence of protein, erythrocytes and leucocytes in the urine, as well as measuring serum creatine concentration, are the appropriate functional screening tests for renal parenchymal disease. These tests should be performed in all patients with hypertension. Renal parenchymal disease may be excluded if urinalysis and serum creatine concentration are normal on repeated determinations. The presence of erythrocytes and leucocytes should be confirmed by microscopic examination of the urine. If the screening tests for renal parenchymal hypertension are positive, a detailed work-up for kidney disease should ensue.

Renovascular hypertension
Renovascular hypertension is the second most common cause of secondary hypertension. In about 75% of the patients, the renal artery stenosis is caused

by atherosclerosis (particularly in the elderly population). Fibromuscular dysplasia accounts for up to 25% of total cases (and is the most common variety in young adults). Signs of renal artery stenosis are an abdominal bruit with
lateralization, hypokalaemia, polyglobulia, and progressive decline in renal function. However, these signs are not present in many patients with renovascular hypertension. An abdominal bruit, for instance, is heard in only about 40% of the patients with renal artery stenosis. Determination of the longitudinal diameter of the kidney using ultrasound can be used as a screening procedure. However, a difference of more

than 1.5 cm in length between the two kidneys which is usually considered as being diagnostic for renal artery stenosis is only found in about 6070% of
the patients with renovascular hypertension. Colour Doppler sonography with calculation of peak systolic velocity and resistance indices in the renal artery is able to detect stenoses of the renal artery, particularly those localized close to the origin of the vessel. In experienced hands, the technique has high sensitivity and specificity, but the procedure is highly observerdependent. There is evidence that investigations of the renal vasculature by breath-hold three-dimensional, gadolinium-enhanced magnetic resonance angiography may become the diagnostic procedure of choice for renovascular hypertension in the future. Some authors report that the sensitivity of this method is over 95%. Another imaging procedure with similar sensitivity is spiral computed tomography, which requires the application of iodine-containing contrast media and the use of relatively high X-ray doses. Once there is a strong suspicion of renal artery stenosis, intraarterial digital subtraction angiography should be performed for confirmation. This invasive procedure is still the gold standard for the detection of renal artery stenosis. The determination of the renal vein rennin ratio requires catheterization of both renal veins and simultaneous sampling from each renal vein and from the inferior vena cava. Despite some claims to the contrary, this test has not achieved acceptable sensitivity or specificity and cannot be recommended as a screening procedure. There are more data supporting its value to assess the functional significance of a renal artery stenosis noted on arteriography, but the matter is still controversial.

Pheochromocytoma

Pheochromocytoma is a very rare form of secondary hypertension. The determination of catecholamines (noradrenalin and adrenaline) as well as of metanephrines in several 24-h urine samples is a reliable method for detection of the disease. The sensitivity of the method is well above 95%. In most patients with phaeochromocytoma, the excretion of noradrenalin, adrenaline, normetanephrine and metanephrine is so elevated that no further confirmation is required. If the urinary excretion of catecholamines and their metabolites is only marginally increased, or normal, despite a strong clinical suspicion of pheochromocytoma, the glucagon stimulation test can be applied. This test requires the measurement of catecholamines in plasma and should be performed after the patient has been effectively treated with a blocker. This pretreatment prevents marked blood pressure rises after the injection of glucagon. The clonidine suppression test also requires the determination of plasma catecholamines. This test is used to identify patients with essential hypertension with increased activity of the sympathetic nervous system causing slight elevations of the excretion of catecholamines and their metabolites in urine. Once the diagnosis of pheochromocytoma has been established, localization of the tumor is necessary. As pheochromocytoma is often big and localized in or in close proximity of the adrenal glands, they are often detected by ultrasound. A more sensitive imaging procedure is computer tomography. The metaiodobenzylguanidine (MIBG) scan is useful in localizing extra-adrenal pheochromocytoma and metastases of the 10% of pheochromocytoma that are malignant. Coarctation of the aorta Coarctation of the aorta is a rare form of hypertension in children and young adults. The diagnosis is usually evident from physical examination. A midsystolic murmur, which may become continuous with time, is heard over the anterior part of the chest and also over the back. The femoral pulse is delayed relative to the radial pulse. Hypertension is found in the upper extremities concomitantly with low or unmeasurable pressures in the legs.

Primary aldosteronism

The determination of serum potassium levels is considered to be a screening test for the disease. However, only about 80% of the patients have hypokalaemia in an early phase, and some authorities maintain that hypokalaemia may even be absent in severe cases. Particularly in patients with bilateral adrenal hyperplasia, serum potassium levels may be normal or only slightly decreased. The diagnosis is con-firmed [after withdrawal of drugs influencing renin, such as -blockers, angiotensin-converting enzyme (ACE) inhibitors, angiotensin receptor antagonists and diuretics] by a low plasma renin activity (<1 ng/ml per hour) and elevated plasma aldosterone levels. A plasma aldosterone (ng/dl): plasma renin activity (ng/ml per hour) >50 is highly suggestive of primary aldosteronism. The diagnosis of primary aldosteronism is con-firmed by the fludrocortisones suppression test: in the presence of primary aldosteronism 4-day administration of fludrocortisones further suppresses plasma renin activity without suppressing plasma aldosterone below a threshold value (5 ng/dl). Imaging procedures such as computer tomography and magnetic resonance imaging are used to localize an aldosterone-producing tumor, but adrenal morphology correlates poorly with function, and adrenal venous sampling, although invasive and difficult to perform, is considered by some investigators as a more reliable procedure. Cushings syndrome Hypertension is a very common finding in Cushings syndrome, affecting about 80% of such patients. The syndrome is often suggested by the typical body habitus of the patient. The determination of 24-h urinary cortisol excretion is the most practical and reliable index of cortisol secretion and a value exceeding 110 nmol (40 g) is highly suggestive of the syndrome. The diagnosis is confirmed by the 2-day, low-dose dexamethasone suppression test (0.5 mg every 6 h for eight doses) or the overnight dexamethasone suppression test (1 mg at 2300 h). In the 2-day test, urinary cortisol excretion higher than 27 nmol (10 g) per day on day two indicates Cushings syndrome. The same is true if plasma cortisol concentration is greater than 140 nmol/l (5 g/dl) at 0800 h in the overnight test. A normal result in either of the two suppression tests excludes the possibility of Cushings syndrome. Further tests and imaging procedures have to be used to differentiate the various forms of the syndrome.

CHOOSING DRUGS FOR PATIENTS NEWLY DIAGNOSED WITH ESSENTIAL HYPERTENSION:

Pharmacological interventions Patients newly diagnosed with essential hypertension who either: 1. have persistent high blood pressure of 160/100 mmHg or more, or
2. are at raised cardiovascular risk with persistent blood pressure of more than 140/90 mmHg (raised cardiovascular risk is defined as a 10-year risk of CVD 20% or existing cardiovascular disease or target organ damage)

are offered drug therapy.

STEP 1
Patients newly diagnosed with essential hypertension who are aged 55 or older, or black and any age, are offered a calcium-channel blocker () or a thiazide-type diuretic (D) as the first choice for initial drug therapy or Patients newly diagnosed with essential hypertension who are younger than 55, and not black, are offered an ACE inhibitor (or angiotensin-II receptor antagonist if ACE inhibitor is not tolerated)

STEP II
ACE inhibitor + calcium-channel blocker or ACE inhibitor + thiazide-type diuretic

STEP III
ACE inhibitor + () + (D)

STEP IV
Add Further diuretic therapy or Alfa-blocker or Beta-blocker Considering seeking specialist advice. P.S. Beta-blockers are not a preferred initial therapy for hypertension but are an alternative to ACE inhibitor in patients younger than 55 years in whom ACE inhibitor is not tolerated or is contraindicated.